Ha Dong Jun, Park Jisun, Seo Go Hun, Lee Kyoungyeul, Kwon Young Se, Lee Ji Eun, Kim Su Jin
Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, South Korea.
Northwest Gyeonggi Regional Center for Rare Disease, Inha University Hospital, Incheon, Korea.
Front Genet. 2022 Mar 11;13:729980. doi: 10.3389/fgene.2022.729980. eCollection 2022.
Infantile cerebellar-retinal degeneration (ICRD) is an extremely rare, infantile-onset neuro-degenerative disease, characterized by autosomal recessive inherited, global developmental delay (GDD), progressive cerebellar and cortical atrophy, and retinal degeneration. In 2012, a biallelic pathogenic variant in gene (NM_001098.3) was found to be causative of this disease. To date, approximately 44 variants displaying various clinical features have been reported. Here, we report a case of two siblings with compound heterozygous variants in the gene. Two siblings without perinatal problems were born to healthy non-consanguineous Korean parents. They showed GDD and seizures since infancy. Their first brain magnetic resonance imaging (MRI), electroencephalography, and metabolic workup revealed no abnormal findings. As they grew, they developed symptoms including ataxia, dysmetria, poor sitting balance, and myopia. Follow-up brain MRI findings revealed atrophy of the cerebellum and optic nerve. Through exome sequencing of both siblings and their parents, we identified the following compound heterozygous variants in the : c.85C > T (p.Arg29Trp) and c.2303C > A (p.Ala768Asp). These two variants were categorized as likely pathogenic based on ACMG/AMP guidelines. In conclusion, this case help to broaden the genetic and clinical spectrum of the variants associated with ICRD. We have also documented the long-term clinical course and serial brain MRI findings for two patients with this extremely rare disease.
婴儿小脑视网膜变性（ICRD）是一种极其罕见的婴儿期发病的神经退行性疾病，其特征为常染色体隐性遗传、全面发育迟缓（GDD）、进行性小脑和皮质萎缩以及视网膜变性。2012年，发现基因（NM_001098.3）中的双等位基因致病变异是该病的病因。迄今为止，已报道了约44种表现出各种临床特征的变异。在此，我们报告一例该基因存在复合杂合变异的两兄弟病例。两名无围产期问题的兄弟由健康的非近亲韩国父母所生。他们自婴儿期起就表现出全面发育迟缓及癫痫发作。他们的首次脑磁共振成像（MRI）、脑电图和代谢检查均未发现异常。随着他们长大，出现了共济失调、辨距不良、坐位平衡差和近视等症状。后续脑MRI检查结果显示小脑和视神经萎缩。通过对两兄弟及其父母进行外显子组测序，我们在该基因中鉴定出以下复合杂合变异：c.85C>T（p.Arg29Trp）和c.2303C>A（p.Ala768Asp）。根据美国医学遗传学与基因组学学会（ACMG）/分子病理学会（AMP）指南，这两个变异被归类为可能致病。总之，该病例有助于拓宽与ICRD相关的该基因变异的遗传和临床谱。我们还记录了两名患有这种极其罕见疾病患者的长期临床病程及系列脑MRI检查结果。
